Monday, June 04, 2007

Calorie restriction and life span extension

We are getting closer to knowing the specific chemical pathways that underlie age extension, at least in nematodes. Similar pathways are found in yeast and higher animals..from the editor's summary in Nature:
Severe calorie restriction extends life-span in mice and other species, but how near-starvation can prolong life remained a mystery. Now at last, specific links between calorie restriction and longevity have been found in that workhorse of ageing research, the nematode C. elegans. Nicholas Bishop and Leonard Guarente find that dietary restriction activates transcription factor SKN-1 in ASI neurons in the head, which signal peripheral tissues to increase metabolic activity, a mechanism suggestive of the involvement of an endocrine system. Panowski et al. report that increased activity of PHA-4, a transcription factor found in the intestine and in a few cells in head and tail, is also essential for diet-restricted longevity. PHA-4 resembles mammalian Foxa transcription factors, which affect development and regulate fasting glucagon and glucose levels. Knowledge of such links raises the prospect of drugs to mimic the benefits of calorie restriction.

From the review by Antebi:

In response to dietary restriction, the activities of SKN-1 and PHA-4 gene-transcription factors increase (black arrows). Neuronal, but not intestinal, SKN-1 mediates longevity in response to reduced dietary intake, where it triggers the release of unidentified hormones (stars) from the pair of ASI neurons to increase mitochondrial activity throughout the body. The PHA-4 transcription factor may also induce hormonal production in the tissues where it is expressed — neurons, intestine and gonad.

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